 |
| Article |
| Hearing impairment and neurological dysfunction associated with a mutation in the mitochondrial tRNASer(UCN) gene |
|
| Kristien Verhoeven1, Robbert JH Ensink2, Valeria Tiranti3, Patrick LM Huygen2, David F Johnson4, Isabelle Schatteman1, Lut Van Laer1, Margriet Verstreken1, Paul Van de Heyning5, Nathan Fischel-Ghodsian4, Massimo Zeviani3, Cor WRJ Cremers2, Patrick J Willems1 and Guy Van Camp1,a |
|
1Department of Medical Genetics, University of Antwerp (UIA), Belgium
2Department of Otolaryngology, University Hospital Nijmegen, The Netherlands
3Division of Biochemistry and Genetics, National Neurological Institute 'Carlo Besta', Milan, Italy
4Medical Genetics Birth Defects Center, Departments of Medicine and Pediatrics, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, CA, USA
5ENT Department, University Hospital of Antwerp, Belgium
|
|
aCorrespondence: Guy Van Camp, Department of Medical Genetics, University of Antwerp (UIA), Universiteitsplein 1, 2610 Wilrijk, Belgium. Tel: 00 32 3 8202570; Fax: 00 32 3 8202566; E-mail: gvcamp@uia.ua.ac.be |
|
| Abstract |
| We studied a large Dutch family with maternally inherited, progressive, sensorineural hearing loss in 27 patients. Only in a single family member was the hearing loss accompanied by neurological symptoms including ataxia and dysarthria. DNA analysis of the mitochondrial genome revealed the insertion of a C at nucleotide position 7472 in the tRNASer(UCN) gene (7472insC mutation). We determined the percentage of mutant DNA (heteroplasmy) in blood from all family members, and found no correlation between hearing loss and leucocyte heteroplasmy. The 7472insC mutation was previously identified in a smaller family from Sicily with sensorineural hearing loss in 9 family members, six of them also presenting neurologically with ataxia and myoclonus. The presence of the 7472insC mutation in two different pedigrees strongly supports its pathogenicity. However, the interfamilial difference in penetrance of the neurologic abnormalities is most likely to be strongly influenced by secondary factors different from the 7472insC mutation, as heteroplasmy or age of the patients were similar in both families. This mutation should therefore be analysed in families with maternally inherited hearing loss, irrespective of whether the hearing loss is non-syndromic or accompanied by neurologic abnormalities. |
|
| Keywords |
| hearing impairment; transfer RNASer(UCN); mitochondrial DNA; heteroplasmy; ototoxicity |
|
|
|
|
| Received 30 January 1998; revised 15 June 1998; accepted 19 June 1998 |
|
| January 1999, Volume 7, Number 1, Pages 45-51 |
| Table of contents Previous Abstract Next Article PDF |
|
